1. Field of the Invention
The present invention relates to a dispensing device for dispensing a preferably medical formulation, in particular containing or consisting of a drug, as a spray including fine particles, wherein the dispensing device is adapted to receive or comprises a storage device with preferably multiple separate and pre-metered doses of the formulation to a storage device for a preferably medical formulation, and to a method for dispensing a preferably medical formulation, in particular containing or consisting of a drug or mixture of drugs, as a spray including fine particles from a storage device having multiple separate and pre-metered doses of the formulation.
2. Description of Related Art
Drugs delivered through dispensing devices, in particular inhalers, are intended to optimally target specific sites in the pulmonary system. These sites include the nasal passages, the throat, and various locations within the lungs, such as the bronchi, bronchioles and alveolar regions. The ability to deliver drugs to a target area depends inter alia on the aerodynamic sizes of the particles or droplets. As currently believed to be understood, particles having an aerodynamic diameter of less than 2 μm are considered to be potentially optimal for deposition in the alveolar region of the lung. Particles that have an aerodynamic diameter of between 2 and approximately 5 μm may be more suitable for delivery to the bronchiole or bronchi regions. Particles with an aerodynamic size range greater than 6 μm, and more preferably 10 μm, are typically suitable for delivery to the laryngeal region, throat or nasal passages.
In most cases, it is desired to achieve a high inhalable fraction and a high delivery efficiency, i.e., the fraction of the initial dose of drug that reaches the desired region, in particular, in the lung. This depends on various factors, in particular, on the characteristics of the generated spray plume, such as propagation velocity of the plume, particle size and its distribution, fraction of small particles, fraction of gas or the like. In the present invention, the desired spray plume characteristics include preferably a small particle size, a high fraction of drug particles with a diameter of 6 μm or less, a low propagation velocity and/or a long duration of spray generation and possible inhalation.
The present invention relates to the dispensing of a preferably medical formulation. The term “formulation” relates, in particular, to a powder, but may include or relate to a liquid as well. Consequently, the fine “particles” may be either solid or liquid. The term “liquid” is to be understood preferably in a broad sense as covering, inter alia, solutions, suspensions, suslutions, mixtures thereof or the like. More particularly, the present invention relates to the dispensing of formulations for inhalation, such as medical formulations containing or comprised of at least one drug.
In the following, the description will focus mainly on powder formulations. However, the same applies for liquid formulations.
In particular, the present invention is concerned with dry powder inhalers for the delivery of drugs to the lungs. Many dry powder inhalers are on the market or have been proposed. There are two main types, namely the passive ones and the active ones. In passive inhalers, all the energy required for de-agglomerating the powder and transferring the powder to the lungs is provided by the breathing of a user, respectively the patient. In active inhalers, there is an additional source of energy to help to de-agglomerate the powder.
Most powder inhalers are of the passive type where the powder is inhaled by the patient without the aid of an additional energy source. The problem with passive inhalers is that the inhalable fraction, or the proportion of powder that actually enters the lungs, is largely dependent on the breathing of the patient. The de-agglomeration of the powder and hence the inhalable fraction is a function of the flow rate of inhaled air through the device and, therefore, varies greatly from patient to patient.
Dry powder inhalers are subdivided into single dose and multi-dose devices or inhalers. Multi-dose inhalers are further subdivided into pre-metered types where the doses are stored individually and into metering inhalers where each powder dose is metered in the device.
Multi-dose pre-metered inhalers have the advantage that the single doses are metered under strict factory conditions and the powder can quite easily be isolated from the atmosphere. In many applications, the active drug powder is mixed with a carrier, such as lactose, which tends to absorb humidity from the atmosphere which makes it stick together and difficult to de-agglomerate.
The present invention relates in particular to an active, gas (preferably air) powered, pre-metered multi-dose dispensing device for dispensing a formulation containing or comprised of a drug, such as a dry powder inhaler.
U.S. Pat. No. 4,627,432 discloses a device for administering medicaments to patients, namely an inhaler. The inhaler comprises a disk-like blister pack having a plurality of blister pockets arranged in a circle. Each blister pocket contains a dose of the powder. A plunger can open a blister pocket. When a blister is opened, the medicament can be withdrawn by a patient inhaling through a mouthpiece.
It is difficult to empty the respective blister pocket completely during a dispensing operation. Incomplete emptying results in decreased delivery efficiency. Some powder may be lost in the inhaler and not dispensed because the known solutions require relatively long paths for the powder until the powder reaches a nozzle and is actually dispensed. This might reduce the delivery efficiency further in addition, de-agglomeration of the powder is difficult and the powder may block an outlet nozzle that is used for dispensing multiple doses one after the other.